15 results on '"Paweł Lenartowicz"'
Search Results
2. Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties
- Author
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Paweł Lenartowicz, Mateusz Psurski, Aleksandra Kotynia, Aleksandra Pieniężna, Monika Cuprych, Klaudia Poniatowska, Justyna Brasuń, and Paweł Kafarski
- Subjects
dehydrocysteine ,dehydropeptides ,addition-elimination reaction ,complexing agent ,antiproliferative activity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.
- Published
- 2021
- Full Text
- View/download PDF
3. Crystal structure of N-(tert-butoxycarbonyl)phenylalanyldehydroalanine isopropyl ester (Boc–Phe–ΔAla–OiPr)
- Author
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Paweł Lenartowicz, Maciej Makowski, Bartosz Zarychta, and Krzysztof Ejsmont
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crystal structure ,dehydro peptides ,α,β-dehydroamino acids ,dehydroalanine ,herringbone packing ,Crystallography ,QD901-999 - Abstract
In the title compound, the dehydrodipeptide (Boc–Phe–ΔAla–OiPr, C20H28N2O5), the molecule has a trans conformation of the N-methylamide group. The geometry of the dehydroalanine moiety is to some extent different from those usually found in simple peptides, indicating conjugation between the H2C=C group and the peptide bond. The bond angles around dehydroalanine have unusually high values due to the steric hindrance, the same interaction influencing the slight distortion from planarity of the dehydroalanine. The molecule is stabilized by intramolecular interactions between the isopropyl group and the N atoms of the peptide main chain. In the crystal, an N—H...O hydrogen bond links the molecules into ribbons, giving a herringbone head-to-head packing arrangement extending along the [100] direction. In the stacks, the molecules are linked by weak C—H...O hydrogen-bonding associations.
- Published
- 2014
- Full Text
- View/download PDF
4. Crystal structure of N-(tert-butoxycarbonyl)glycyl-(Z)-β-bromodehydroalanine methyl ester [Boc–Gly–(β-Br)(Z)ΔAla–OMe]
- Author
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Paweł Lenartowicz, Maciej Makowski, Bartosz Zarychta, and Krzysztof Ejsmont
- Subjects
crystal structure ,β-bromodehydroalanine ,dehydroamino acid ,non-helical conformation ,hydrogen bonding ,Crystallography ,QD901-999 - Abstract
The title compound, C11H17BrN2O5, is a dehydroamino acid with a C=C bond between the α- and β-C atoms. The amino acid residues are linked trans to each other and there are no strong intramolecular hydrogen bonds. The torsion angles indicate a non-helical conformation of the molecule. The dipeptide folding is influenced by an intermolecular N—H...O hydrogen bond and also minimizes steric repulsion. In the crystal, molecules are linked by strong N—H...O hydrogen bonds, generating (001) sheets. The sheets are linked by weak C—H...O and C—H...Br bonds and short Br...Br [3.4149 (3) Å] interactions.
- Published
- 2014
- Full Text
- View/download PDF
5. Novel, automated, semi-industrial modular photobioreactor system for cultivation of demanding microalgae that produce fine chemicals - The next story of H. pluvialis and astaxanthin
- Author
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Jacek Lipok, Paweł Lenartowicz, Michał Grzebyk, Daniel Borowiak, Paweł Kafarski, and Maciej Wiśniewski
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0301 basic medicine ,020209 energy ,Cultivation ,Biomass ,Photobioreactor ,02 engineering and technology ,03 medical and health sciences ,chemistry.chemical_compound ,Astaxanthin ,Haematococcus ,0202 electrical engineering, electronic engineering, information engineering ,Bioreactor ,Microalgae ,Process engineering ,biology ,business.industry ,Scale (chemistry) ,Process automation system ,biology.organism_classification ,030104 developmental biology ,chemistry ,Scientific method ,Environmental science ,Process control ,Haematococcus pluvialis ,Semi-technical scale ,business ,Agronomy and Crop Science - Abstract
Recently, there has been increased interest in the use of microorganisms in the production of pharmaceuticals, nutraceuticals and energy supply products, which is due to their rapid growth rate and ability to biosynthesize fine chemicals or biotransform specific xenobiotics. To achieve the desired scale of production and optimization of microbial cultures, it is necessary to design bioreactors that enable process automation, control of working parameters, reduction of microbial and chemical contaminations, and culture independence of climate conditions. In response to this need, an original, modular airlift-type photobioreactor system was designed and manufactured. This novel semitechnical system, with a total volume of 1000 dm3, was operated via computer control, which enabled the creation of time profiles of red, blue and white LED illumination and of carbon dioxide and air dosing. The quality and usefulness of the developed system was demonstrated via the case study, namely two-stage cultivation of the microalgae Haematococcus pluvialis—a species commonly used in the production of natural astaxanthin. The experimentally developed procedure ensures a repeatable and efficient biomass multiplication process and the maintenance of a light- and chemical-mediated effective stress mechanism that allows the production of up to 3.2% natural astaxanthin in terms of dry biomass.
- Published
- 2021
6. A novel approach for obtaining α,β-diaminophosphonates bearing structurally diverse side chains and their interactions with transition metal ions studied by ITC
- Author
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Paweł Lenartowicz, Błażej Dziuk, Paweł Kafarski, Beata Żyszka-Haberecht, Danuta Witkowska, Jolanta Świątek-Kozłowska, and Krzysztof Ejsmont
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Nickel ,chemistry ,010405 organic chemistry ,General Chemical Engineering ,Side chain ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Copper ,Transition metal ions ,0104 chemical sciences - Abstract
Aminophosphonates are an important group of building blocks in medicinal and pharmaceutical chemistry. Novel representatives of this class of compounds containing nontypical side chains are still needed. The aza-Michael-type addition of amines to phosphonodehydroalanine derivatives provides a simple and effective approach for synthesizing N′-substituted α,β-diaminoethylphosphonates and thus affords general access to aminophosphonates bearing structurally diverse side chains. Thermodynamic analysis of the chosen aminophosphonates at physiological pH proves that they serve as potent chelators for copper(II) ions and moderate chelators for nickel(II) ions.
- Published
- 2020
7. Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties †
- Author
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Mateusz Psurski, Klaudia Poniatowska, Paweł Lenartowicz, Aleksandra Pieniężna, Justyna Brasuń, Aleksandra Kotynia, Monika Cuprych, and Paweł Kafarski
- Subjects
antiproliferative activity ,BALB 3T3 Cells ,Double bond ,Potentiometric titration ,Sulforhodamine B ,Triazole ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Catalysis ,Article ,lcsh:Chemistry ,Inorganic Chemistry ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Elimination reaction ,Cell Line, Tumor ,Animals ,Humans ,Chelation ,Cysteine ,Physical and Theoretical Chemistry ,dehydrocysteine ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Cell Proliferation ,chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Chemical modification ,Dipeptides ,General Medicine ,Hydrogen-Ion Concentration ,Combinatorial chemistry ,Enzymes ,0104 chemical sciences ,Computer Science Applications ,dehydropeptides ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,complexing agent ,addition-elimination reaction ,Drug Screening Assays, Antitumor ,Copper ,Conjugate - Abstract
Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.
- Published
- 2021
8. Analytical procedures for short chain chlorinated paraffins determination - How to make them greener?
- Author
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Paweł Lenartowicz, Jacek Namieśnik, Kaja Kalinowska, and Mariusz Marć
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Gas chromatography ,Environmental Engineering ,010504 meteorology & atmospheric sciences ,Computer science ,Process (engineering) ,Green analytical chemistry ,media_common.quotation_subject ,Sample preparation techniques ,Short-chain chlorinated paraffins ,010501 environmental sciences ,01 natural sciences ,Pollution ,Results quality ,Qualitative analysis ,Chlorinated paraffins ,Environmental samples ,Environmental Chemistry ,Analytical procedures ,Quality (business) ,Biochemical engineering ,Waste Management and Disposal ,Reliability (statistics) ,0105 earth and related environmental sciences ,media_common - Abstract
The aim of the following paper was to gather current scientific information about the analytical protocols dedicated to measuring the content level of short-chain chlorinated paraffins (SCCPs) in various types of environmental samples. Moreover, the data about the basic validation parameters of applied procedures for SCCPs determination are listed. The main issue which is highlighted in the paper is the possibility of the application of green analytical chemistry (GAC) principals in the SCCPs measuring process to reduce the environmental impact of the applied methodology. Analytical methods dedicated to SCCPs determination contain a significant number of steps and require advanced analytical equipment during the quantitative and qualitative analysis. In addition, there is a substantial issue associated with the reliability of the obtained results, especially in the case of the quantification of individual SCCPs in the studied samples. Due to this fact, the paper attempts to discuss the various stages of the analytical procedure, in which appropriate changes in the formula or equipment solutions might be introduced to ensure a better quality of the analytical results, as well as to meet the requirements of the philosophy of green analytical chemistry. The most important case which concerns this subject is finding an optimal consensus between the economic and logistic aspects and the quality and “greenness” of the analytical procedure employed in SCCPs determination process.
- Published
- 2019
9. Access to α-Aminophosphonic Acid Derivatives and Phosphonopeptides by [Rh(P–OP)]-Catalyzed Stereoselective Hydrogenation
- Author
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Arnald Grabulosa, Héctor Fernández-Pérez, Lucas Carreras, Paweł Kafarski, Paweł Lenartowicz, and Anton Vidal-Ferran
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010405 organic chemistry ,Chemistry ,Ligand ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,0104 chemical sciences ,Catalysis ,Rhodium ,Derivative (finance) ,Molecule ,Stereoselectivity - Abstract
The hydrogenation of N-substituted vinylphosphonates using rhodium complexes derived from P–OP ligands L1, ent-L1, or (R,R)-Me-DuPHOS as catalysts has been successfully accomplished, achieving very high levels of stereoselectivity (up to 99% ee or de). The described synthetic strategy allowed for the efficient preparation of α-aminophosphonic acid derivatives and phosphonopeptides, which are valuable building blocks for the preparation of biologically relevant molecules.
- Published
- 2020
10. The overproduction of 2,4-DTBP accompanying to the lack of available form of phosphorus during the biodegradative utilization of aminophosphonates by Aspergillus terreus
- Author
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Paweł Kafarski, Paweł Lenartowicz, and Jacek Lipok
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Environmental Engineering ,Magnetic Resonance Spectroscopy ,Organophosphonates ,chemistry.chemical_element ,Bioengineering ,Context (language use) ,Fungus ,Microbiology ,Gas Chromatography-Mass Spectrometry ,Phenols ,Environmental Chemistry ,Aspergillus terreus ,4-di-tert-butylphenol ,Biomass ,skin and connective tissue diseases ,Overproduction ,biology ,Phosphorus ,filamentous fungi ,Metabolism ,Biodegradation ,biology.organism_classification ,Pollution ,Culture Media ,Aspergillus ,Biodegradation, Environmental ,Biochemistry ,chemistry ,phosphonate utilization - Abstract
Although information about the ability of some filamentous fungi to biodegrade organophosphonates is available, the knowledge about accompanying changes in fungal metabolism is very limited. The aim of our study was to determine the utilization of the chosen, structurally diverse aminophosphonates by Aspergillus terreus (Thom), in the context of the behaviour of this fungus while growing in unfavourable conditions, namely the lack of easily available phosphates. We found that all the studied compounds were utilized by fungus as nutritive sources of phosphorus, however, their effect on the production of fungal biomass depended on their structure. We also observed an interesting change in the metabolism of A. terreus; namely the overproduction of 2,4-di-tert-butylphenol (2,4-DTBP), which is known to possess fungistatic activity. In the case of our study, the biosynthesis of this compound was induced by phosphorus starvation, caused either by the lack of that element in the medium, or the poor degradation of phosphonate.
- Published
- 2015
11. Synthesis of dehydrodipeptide esters and their evaluation as inhibitors of cathepsin C
- Author
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Maciej Makowski, Paweł Lenartowicz, Bartosz Oszywa, Paweł Kafarski, Michał Jewgiński, and Małgorzata Pawełczak
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chemistry.chemical_classification ,Molecular model ,molecular modeling ,esterification ,enzyme inhibitors ,Pharmacology toxicology ,Organic Chemistry ,humanities ,Cathepsin C ,chemistry.chemical_compound ,Pharmacology, Toxicology and Pharmaceutics(all) ,Enzyme ,dehydropeptides ,chemistry ,Biochemistry ,Dehydroalanine ,General Pharmacology, Toxicology and Pharmaceutics ,Original Research - Abstract
The procedures for the synthesis of esters of dehydropeptides containing C-terminal (Z)-dehydrophenylalanine and dehydroalanine have been elaborated. These esters appeared to be moderate or weak inhibitors of cathepsin C, with some of them exhibiting slow-binding behavior. As shown by molecular modeling, they are rather bound at the surface of the enzyme and are not submersed in its binding cavities. Electronic supplementary material The online version of this article (doi:10.1007/s00044-015-1366-0) contains supplementary material, which is available to authorized users.
- Published
- 2015
12. Crystal structure of N-(tert-butoxycarbonyl)phenylalanyldehydroalanine isopropyl ester (Boc–Phe–ΔAla–OiPr)
- Author
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Bartosz Zarychta, Maciej Makowski, Krzysztof Ejsmont, and Paweł Lenartowicz
- Subjects
Steric effects ,dehydroalanine ,crystal structure ,dehydro peptides ,Crystal structure ,Research Communications ,lcsh:Chemistry ,chemistry.chemical_compound ,Dehydroalanine ,α,β-dehydroamino acids ,Peptide bond ,Moiety ,General Materials Science ,Hydrogen bond ,[alpha] ,General Chemistry ,dehydroalanine ,dehydro peptides ,Condensed Matter Physics ,herringbone packing ,[beta]-dehydroamino acids ,Crystallography ,Molecular geometry ,chemistry ,lcsh:QD1-999 ,α,β-dehydroamino acids ,Isopropyl - Abstract
In the crystal structure of the dehydrodipeptide (Boc-Phe-ΔAla-OiPr), the molecule has a trans configuration of the N-methylamide group. Its geometry is different from saturated peptides but is in excellent agreement with other dehydroalanine compounds. In the crystal, an N—H⋯O hydrogen bond links the molecules in a herringbone packing arrangement., In the title compound, the dehydrodipeptide (Boc–Phe–ΔAla–OiPr, C20H28N2O5), the molecule has a trans conformation of the N-methylamide group. The geometry of the dehydroalanine moiety is to some extent different from those usually found in simple peptides, indicating conjugation between the H2C=C group and the peptide bond. The bond angles around dehydroalanine have unusually high values due to the steric hindrance, the same interaction influencing the slight distortion from planarity of the dehydroalanine. The molecule is stabilized by intramolecular interactions between the isopropyl group and the N atoms of the peptide main chain. In the crystal, an N—H⋯O hydrogen bond links the molecules into ribbons, giving a herringbone head-to-head packing arrangement extending along the [100] direction. In the stacks, the molecules are linked by weak C—H⋯O hydrogen-bonding associations.
- Published
- 2014
13. Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C
- Author
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Bartosz Oszywa, Rafał Latajka, Małgorzata Pawełczak, Paweł Lenartowicz, Maciej Makowski, Kinga Haremza, and Paweł Kafarski
- Subjects
0301 basic medicine ,Models, Molecular ,Double bond ,Stereochemistry ,Phenylalanine ,Cysteine Proteinase Inhibitors ,Biochemistry ,Cathepsin C ,Substrate Specificity ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,Dehydroalanine ,Moiety ,Animals ,Sulfhydryl Compounds ,Binding site ,chemistry.chemical_classification ,Dipeptide ,Alanine ,Binding Sites ,Dehydropeptides ,Diastereomer ,Enzyme inhibitors ,General Medicine ,Dipeptides ,Kinetics ,030104 developmental biology ,chemistry ,Thiol addition ,030220 oncology & carcinogenesis ,Cattle - Abstract
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors. This was proved by TLC analysis of the medium in which interaction of methyl (S)-phenylalanyl-(R,S)-(S-adamantyl)cysteinate (7i) with the enzyme was studied. Molecular modeling enabled to establish their mode of binding showed that S2 pocket is long and narrow and accommodates phenyl group of phenylalanine while significantly spacious sites located at the surface of the enzyme (one of them being S1 pocket) bind the adamantly moiety oriented in different direction for each stereoisomer. Finally replacement of carboxymethyl moitey of methyl (S)-phenylalanyl-(R,S)-(S-phenyl)cysteinate (7c) with nitrile group provided about 650-times more potent inhibitor of cathepsin C indicating that the studied C-terminal S-substituted cysteines are good activity probes for S1 binding pocket of this enzyme.
- Published
- 2017
14. Michael additions to double bonds of esters of N-protected (s)-phenylalanyldehydroalanine (X-(s)-Phe-ΔAla-OMe) and its phosphonic acid counterpart (X-(s)-Phe-ΔAla-PO(OEt)2)
- Author
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Paweł Kafarski, Błażej Dziuk, Maciej Makowski, Bartosz Zarychta, and Paweł Lenartowicz
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chemistry.chemical_classification ,phosphonopeptides ,dehydrodipeptides ,Double bond ,010405 organic chemistry ,Electrophilic addition ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,0104 chemical sciences ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Bromide ,Michael addition ,Michael reaction ,dehydrophosphonodipeptides - Abstract
Electrophilic addition of amines, thiols and bromide to the double bonds of model dehydrodipeptides and dehydrophosphonodipeptide was studied. The double bond in these two classes of peptides reacted similarly and gave the same products. These results indicate that dehydropeptides are very good candidates as substrates for modifications of peptide side-chains.
- Published
- 2017
- Full Text
- View/download PDF
15. Crystal structure ofN-(tert-butoxycarbonyl)glycyl-(Z)-β-bromodehydroalanine methyl ester [Boc–Gly–(β-Br)(Z)ΔAla–OMe]
- Author
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Krzysztof Ejsmont, Maciej Makowski, Bartosz Zarychta, and Paweł Lenartowicz
- Subjects
inorganic chemicals ,crystal structure ,Stereochemistry ,education ,Crystal structure ,behavioral disciplines and activities ,Research Communications ,Steric repulsion ,lcsh:Chemistry ,chemistry.chemical_compound ,dehydroamino acid ,β-bromodehydroalanine ,dehydroamino acid ,non-helical conformation ,General Materials Science ,[beta]-bromodehydroalanine ,Amino acid residue ,health care economics and organizations ,Quantitative Biology::Biomolecules ,Dipeptide ,Chemistry ,Hydrogen bond ,General Chemistry ,hydrogen bonding ,Condensed Matter Physics ,humanities ,lcsh:QD1-999 ,β-bromodehydroalanine ,Alanine methyl ester - Abstract
In a dehydroamino acid with a C=C bond between the α- and β-C atoms, the amino acid residues are linked trans to each other and there are no strong intramolecular hydrogen bonds. The torsion angles indicate a non-helical conformation of the molecule., The title compound, C11H17BrN2O5, is a dehydroamino acid with a C=C bond between the α- and β-C atoms. The amino acid residues are linked trans to each other and there are no strong intramolecular hydrogen bonds. The torsion angles indicate a non-helical conformation of the molecule. The dipeptide folding is influenced by an intermolecular N—H⋯O hydrogen bond and also minimizes steric repulsion. In the crystal, molecules are linked by strong N—H⋯O hydrogen bonds, generating (001) sheets. The sheets are linked by weak C—H⋯O and C—H⋯Br bonds and short Br⋯Br [3.4149 (3) Å] interactions.
- Published
- 2014
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